Entacapone Tablets
DEFINITION
Entacapone Tablets contain an amount of entacapone equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of entacapone (C14H15N3O5).
IDENTIFICATION
• A. Infrared Absorption 
197K
:
The sample shows a medium band at about 2216 cm-1 and strong bands at about 2216, 1628, 1604, 1544, 1512, 1440, 1376, 1348, 1296, 1280, and 1208 cm-1 similar to the reference preparation.
197K:
The sample shows a medium band at about 2216 cm-1 and strong bands at about 2216, 1628, 1604, 1544, 1512, 1440, 1376, 1348, 1296, 1280, and 1208 cm-1 similar to the reference preparation.
• B.
The retention time of the major peak from the Sample solution corresponds to that from the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
[Note—Protect solutions from light. ]
Buffer:
2.1 g/L of monobasic sodium phosphate. Adjust with phosphoric acid to a pH of 2.1.
Diluent:
Methanol and tetrahydrofuran (7:3)
Mobile phase:
Methanol, tetrahydrofuran, and Buffer (22:1:27)
Standard solution:
0.5 mg/mL of USP Entacapone RS in Diluent
Sample solution:
0.5 mg/mL of entacapone from finely powdered Tablets (NLT 20). Add tetrahydrofuran up to 30% of the final volume, and sonicate for 3 min. Add methanol up to 30% of the final volume, and shake for 5 min. Dilute with methanol to volume. Centrifuge a portion of this solution.
Chromatographic system
Mode:
LC
Detector:
UV 300 nm
Column:
4.6-mm × 25-cm; 5-µm packing L11
Flow rate:
1 mL/min
Run time:
1.5 times the retention time of the entacapone peak
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 1.5%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C14H15N3O5 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Entacapone RS in the Standard solution (mg/mL) |
| CU | = | = concentration of entacapone in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
pH 5.5 Phosphate buffer (6.8 g/L of monobasic potassium phosphate in water. Adjust with 1 M sodium hydroxide to a pH of 5.5); 900 mL.
Apparatus 2:
50 rpm
Time:
30 min
Standard stock solution:
0.22 mg/mL of USP Entacapone RS, prepared by dissolving in 2% of the flask volume in tetrahydrofuran and diluting with Medium to volume. Protect this solution from the light.
Standard solution:
22 µg/mL of USP Entacapone RS in Medium from the Standard stock solution. Protect this solution from the light.
Sample solution:
Pass a portion of the solution through a suitable filter of 20-µm pore size. Dilute with Medium, if necessary. Protect this solution from the light.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
313 nm
Path length:
1 cm
Blank:
Tetrahydrofuran and Medium (0.2:99.8)
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C14H15N3O5 dissolved:
Result = AU/AS × CS/L × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of C14H15N3O5 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
[Note—Protect solutions from light. ]
Buffer, Diluent, Mobile phase, and Chromatographic system:
Proceed as directed in the Assay.
System suitability solution:
0.03 mg/mL each of USP Entacapone RS and USP Entacapone Related Compound A RS in Diluent
Standard solution:
3 µg/mL of USP Entacapone RS in Diluent
Sample solution:
3 mg/mL of entacapone from finely powdered Tablets (NLT 20). Add tetrahydrofuran up to 30% of the final volume, and sonicate for 3 min. Add methanol up to 30% of the final volume, and sonicate for 5 min. Dilute with methanol to volume. Centrifuge a portion of this solution. [Note—Prepare the Sample solution fresh and use within 7 h of preparation. ]
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between entacapone related compound A and entacapone, System suitability solution
Relative standard deviation:
NMT 10.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of entacapone from the Standard solution |
| CS | = | = concentration of USP Entacapone RS in the Standard solution (mg/mL) |
| CU | = | = concentration of entacapone in the Sample solution (mg/mL) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.2%
[Note—Do not include entacapone related compound A in the calculation of total impurities. ]
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|
| Entacapone related compound Aa | 0.8 | 0.2 | |
| Entacapone | 1.0 | — | |
| Any individual unspecified degradation product | — | 0.1 | |
|
a
(Z)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylacrylamide.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in light-resistant containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Entacapone RS 
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USP Entacapone Related Compound A RS
(Z)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylacrylamide.
C14H15N3O5 305.29
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(Z)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylacrylamide.
C14H15N3O5 305.29
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3048
Pharmacopeial Forum: Volume No. 36(3) Page 667